The overall goal of Project I is to improve the clinical treatment of patients with advanced ovarian cancer through a logically directed chemotherapy program, utilizing our own findings of the past 7 years and new knowledge about chemotherapy mechanisms and resistance. This project outlines the planned clinical efforts of an integrated group incorporating Gynecologic surgeons, medical oncologists, nurses, and a clinical psychologist. The program represents the continuation of Project I from the previous grant periods. It focuses on five inter-related programs, encompassing the treatment of ovarian cancer patients, from the time of initial post operative chemotherapy, through second look surgery and into recurrent disease. The primary chemotherapy strategy is based on a novel approach to risk stratification, dividing the population into good-prognosis patients and poor-prognosis patients, based on CA-125 values midway through treatment. In Specific Aim 1, we present the logical completion of our 7-year series of studies, directed at identifying the role of stem-cell-supported dose- dense therapy with cyclophosphamide, paclitaxel and carboplatin. Based on our studies in this area, we now restrict high-dose therapy to patients with small-volume platinum-sensitive disease. Specific Aim 2 represents a new direction, providing a "therapy window" approach to poor prognosis patients. Through this design, we provide a logical structure to test selected new combinations to minimally pretreated patients. The salvage chemotherapy strategy for small-volume disease (<0.5 cm) is based on Memorial Hospital's longstanding commitment to intraperitoneal chemotherapy. Development of these regimens will be the focus of Specific Aim 3. Specific Aim 4 is a continuation of our interest in CDDP-resistant disease. The proposed trials are largely based on the work of Dr. Spriggs'/Aghajanian's laboratory (detailed in Project II), focusing on approaches to decrease resistance gene activation. This will be patients with bulky disease (>0.5 cm). Our approach to quality of life measures in ovarian cancer is detailed in specific aim 5. This focus on quality of life expresses both our interest in less traditional measures of clinical trial outcomes and a need to quantify the impact of therapy on women who may not be cured by current intervention.